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Respiratory Neurobiology

Physiology and Clinical Disorders, Part I

1st Edition - August 12, 2022

Editors: Robert Chen, Patrice G. Guyenet

Hardback ISBN:

9 7 8 - 0 - 3 2 3 - 9 1 5 3 4 - 2

eBook ISBN:

9 7 8 - 0 - 3 2 3 - 9 1 5 3 5 - 9

Respiratory Neurobiology: Physiology and Clinical Disorders, Part One, Volume 188 is one of two volumes on the neurology of breathing. This volume focuses on the neurophysiology… Read more

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Respiratory Neurobiology: Physiology and Clinical Disorders, Part One, Volume 188 is one of two volumes on the neurology of breathing. This volume focuses on the neurophysiology of breathing, while the second volume focuses on pathologies attributable to abnormalities of the neural control of breathing, breathing problems that may occur in neurological diseases, and the neurological complications of respiratory diseases.

Cover image
Title page
Table of Contents
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Contributors
Chapter 1: Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms
Abstract
Introduction
The Neuromechanical Phases of Breathing and Motor Pattern In Vivo
Brainstem Respiratory Neurons: Nomenclature, Spiking Patterns, and Locations
The Spatial-Functional Architecture and Properties of Brainstem Respiratory Structures
Functional Respiratory Compartments and Local Circuits
Identifying Intrinsic Oscillators in the Respiratory CPG
Inspiratory Rhythm and Pattern Generation in preBötC Excitatory Circuits
Generation of Inspiratory–Expiratory Patterns: Core Circuits and the Inhibitory Connectome
Control of Respiratory Rhythm and Pattern by Modulatory Inputs
Other Interacting Oscillations in Respiratory Pattern Generation
Summary
References
Chapter 2: Central respiratory chemoreception
Abstract
Homeostatic and Other Functions of Central Respiratory Chemoreception
Serotonergic Neurons and CRC
Other Central Respiratory Chemoreceptor Candidates
Relative Contribution of [H+], Molecular CO2, and Bicarbonate to CRC
Conclusions: CRC: Facts, Speculations, and Potential Therapeutic Applications
References
Chapter 3: Neurobiology of the carotid body
Abstract
Introduction
Structural Organization and Innervation of the Carotid Bodies
Carotid Body-Mediated Systemic Responses. Peripheral Chemoreflex
Functional Properties of Chemosensory Glomus Cells
Chemosensory Glomus Cell-Afferent Fiber Synapse. Carotid Body Output
Carotid Body Stem Cells and Progenitor Cells. Role in Plasticity
Carotid Bodies and Mechanisms of Disease
Concluding Remarks
Acknowledgments
References
Chapter 4: Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia
Abstract
Chronic Continuous Hypoxia
Chronic Intermittent Hypoxia
Acknowledgments
References
Chapter 5: Early development of the breathing network
Abstract
Introduction
General Principles of Brainstem Development
Development of the Pontine Respiratory Group
Development of the Dorsal Medullary Respiratory Column
Development of the Ventral Medullary Respiratory Column
Carotid Bodies
Conclusion
Acknowledgments
References
Chapter 6: Critical roles for breathing in the genesis and modulation of emotional states
Abstract
Introduction
Roles of Breathing in the Genesis of Emotion
Neural Structures Common to Breathing and Emotion
Mutual Importance of Breathing and Emotion
Voluntary Control of Breathing as an Essential Practice for Achieving and Maintaining Emotional Well-Being
Conclusions
References
Chapter 7: Breathing during sleep
Abstract
Introduction
Effects on NREM and REM Sleep on Ventilation and the Rate, Depth and Pattern of Breathing
Respiratory Changes during Sleep–Wake State Transitions
Activity of Central Respiratory Neurons across Sleep–Wake States
Wake-Active Neurons and the Wakefulness Stimulus for Breathing
Clinical Trials Based on Studies of Wake-Active Neurons
Sleep-Active Neurons and their Potential Effects on Breathing
Ventilatory Chemosensitivity during Sleep
Mechanisms and Pathways of the Arousal from Sleep Elicited by Chemical Stimulation of Breathing
Conclusions
Acknowledgments
References
Chapter 8: The physiology and pathophysiology of exercise hyperpnea
Abstract
Exercise Hyperpnea in Health
Pathophysiology of Exercise Hyperpnea
General Conclusions
Acknowledgments
References
Chapter 9: Regulation of breathing by cardiopulmonary afferents☆
Abstract
Introduction
Afferent Pathways
Cardiovascular Afferents
Respiratory Afferents
Neuroepithelial Bodies
Vagal Reflex Function
Emergence of New Technology
Interpretation of Some Special Issues
Conclusion
References
Chapter 10: Respiratory–cardiovascular interactions
Abstract
Introduction
Oscillations in the Cardiovascular System
Respiratory Cardiac Coupling
Respiratory Sympathetic Coupling
Concluding Remarks and Some Future Perspectives
Acknowledgments
References
Chapter 11: Dyspnea
Abstract
Introduction
Multiple Forms and Dimensions of Dyspnea
Air Hunger
Perception of Effort to Breathe
The Sensation of Chest Tightness and Asthma
Clinical Management of Air Hunger
Summary
References
Chapter 12: The pathophysiology of opioid-induced respiratory depression
Abstract
Introduction to Opiates and Synthetic Opioids
Physiological Effects of Opioid Drugs
Respiratory Effects of Opioid Drugs
Neural Circuit Responsible for Opioid-Induced Respiratory Depression
Molecular Mechanisms of Opioid-Induced Respiratory Depression
Therapies to Prevent or Reverse Opioid-Induced Respiratory Depression
Conclusion
References
Chapter 13: The sigh and related behaviors
Abstract
Introduction
What Defines a Sigh?
Emotional Sighing
The Sigh as a Reflex
Respiratory Variability and Sighing
Cellular Determinants of Sighing in the CNS
The Association of Sighing With Arousal
Sneezing, Hiccupping, and Yawning
Conclusion
References
Chapter 14: Neural control of the lower airways: Role in cough and airway inflammatory disease
Abstract
Introduction
Sensory Afferent Innervation of the Lower Airways
Autonomic Efferent Innervation of the Lower Airways
Airway Inflammation-Induced Neuromodulation
Role of Airway Nerves in Asthma, Airway Hyperreactivity, COPD, and Chronic Cough
Summary
References
Chapter 15: The phrenic neuromuscular system
Abstract
The Diaphragm
The Phrenic Nerve
Phrenic Motoneurons
Bulbospinal Innervation of the Phrenic Nucleus
Corticospinal Inputs to PhrMNs
Propriospinal Neurons and the Phrenic Motor Circuit
Recruitment of PhrMNs
Summary and Conclusions
References
Chapter 16: Respiratory neuroplasticity: Mechanisms and translational implications of phrenic motor plasticity
Abstract
Introduction
Respiratory Neuroplasticity and Related Phenomena: Definitions
Mechanisms of Respiratory Motor Plasticity
Concluding Remarks: What Does It All Mean?
Sources of funding
References
Index

Robert Chen

Dr. Robert Chen received MA and medical degrees (MBBChir) from the University of Cambridge and M.Sc. from the University of Toronto. He undertook Neurology residency at the Western University, and fellowship at the National Institute of Neurological Disorders and Stroke. He is currently Professor of Medicine (Neurology) at the University of Toronto, the Catherine Manson Chair in Movement Disorders, Senior Scientist at the Krembil Brain Institute, a full member of the Institute of Medical Science at the University of Toronto, Editor-in-Chief of the Canadian Journal of Neurological Sciences and Associate Editor for Movement Disorders. His research interests include human motor physiology, brain plasticity and understanding the pathophysiology and development of new treatments for movement disorders such as Parkinson’s disease and dystonia. He has published over 350 research papers with Google Scholar H-index of over 100.

Affiliations and expertise

Professor of Medicine (Neurology), University of Toronto; Senior Scientist, Krembil Research Institute, Toronto, ONT, Canada

Patrice G. Guyenet

Dr. Guyenet is a neuroscientist, Professor of Pharmacology, with a career spanning 42 years on the faculty of the University of Virginia (UVa) School of Medicine (Charlottesville, VA, USA). Born in France, he received his undergraduate education in the basic sciences at Ecole Normale Supérieure, Paris (1967-1971). He earned a Ph.D. in neuropsychopharmacology from College de France, Paris, under the direction of College de France Professor Jacques Glowinski where his scientific career was launched (1972-1975). This was followed by postdoctoral studies in neurophysiology at Yale University (1976-1978) mentored by Dr. GK Aghajanian. Dr. Guyenet joined the faculty of the University of Virginia School of Medicine, Department of Pharmacology in 1978 pursuing a basic research focus on the autonomic nervous system and breathing. His research is a branch of Integrative Neuroscience, a discipline that seeks to understand how the brain processes specific types of information. The laboratory studies how the mammalian brain regulates respiration and blood pressure, two physiological processes that are dysfunctional in highly prevalent diseases (hypertension, obesity, apneic syndromes, heart failure, etc.). Continuously supported by the National Institutes of Health, Heart, Lung and Blood Institute, his research program has contributed to seminal progress in the field. A key advance has been the characterization of a lower brainstem nucleus that senses pH and maintains blood CO2 constant by adjusting lung ventilation (the retrotrapezoid nucleus). This work has given a new impetus to the study of central respiratory chemoreception, a field that is rapidly growing in the US and elsewhere. Dr. Guyenet and collaborators have published 243 articles in refereed scientific journals, including high impact publications such as Science, Nature, and Nature Neuroscience. His influence in the field is reflected by his scientific impact metrics (h-index 99; 28,000 citations). Dr. Guyenet and his lab have received several awards including the NIH-HLBI Merit Award, the Carl Ludwig Distinguished lecture of the American Physiological Society, 2008, and UVa Distinguished Scientist Award, 2011. Additionally, Dr. Guyenet received the Edlich-Henderson Inventor of the Year Award (1996) along with colleagues J. Jagger, R. Pearson and J. Brand granted in recognition of three patents, two of which were successfully commercialized. Along with research, teaching and mentoring has been integral to Dr. Guyenet’s academic contributions. Over four decades Dr. Guyenet mentored 15 PhDs and 24 postdoctoral scholars, many of whom have faculty positions in the US and elsewhere. He has been rewarded many times over by medical students for his teaching contributions including the Medical School Student Basic Sciences Teaching Awards (9 times) and the UVa Medical School Award for Excellence in Teaching (1995, 2003). Dr. Guyenet is especially grateful to his department chairmen, Drs. J. Larner, J. Garrison and D. Bayliss for their unflagging support and the freedom to seek his own path. Most importantly, he acknowledges the immense debt he owes to his enthusiastic, hard-working, and talented collaborators. Finally, Dr. Guyenet thanks profusely everyone who has contributed to these twin volumes on Respiratory Neurobiology and hopes that the final product will be helpful to clinicians and basic scientists alike, as a scholarly reference or, hopefully, as an inspiration to move the field to new heights.

Affiliations and expertise

Professor of Pharmacology, Emeritus, University of Virginia School of Medicine, Charlottesville, VA, United States